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Free energy calculations in molecular simulations have a variety of applications including determining the strength of molecular processes such as solvation and binding. It has been recently shown that when removing the VDW and Coulomb…

Chemical Physics · Physics 2015-07-15 Asaf Farhi , Bipin Singh

We investigate the optimization of two probabilistic generative models with binary latent variables using a novel variational EM approach. The approach distinguishes itself from previous variational approaches by using latent states as…

Machine Learning · Statistics 2018-02-26 Jörg Lücke , Zhenwen Dai , Georgios Exarchakis

We devise automated workflows for the calculation of Helmholtz and Gibbs free energies and their temperature and pressure dependence and provide the corresponding computational tools. We employ non-equilibrium thermodynamics for evaluating…

Materials Science · Physics 2021-10-13 Sarath Menon , Yury Lysogorskiy , Jutta Rogal , Ralf Drautz

The Alchemical Transfer Method (ATM) for the calculation of standard binding free energies of non-covalent molecular complexes is presented. The method is based on a coordinate displacement perturbation of the ligand between the receptor…

Chemical Physics · Physics 2021-01-21 Joe Z. Wu , Solmaz Azimi , Sheenam Khuttan , Nanjie Deng , Emilio Gallicchio

We propose a method to compute free-energy differences from nonadiabatic alchemical transformations using flow-based generative models. The method, nonadiabatic force matching, hinges on estimating the dissipation along an alchemical…

Chemical Physics · Physics 2025-11-21 Jorge L. Rosa-Raíces , David T. Limmer

We present a new and efficient method for computing the transition pathways, free energy barriers, and transition rates in complex systems with relatively smooth energy landscapes. The method proceeds by evolving strings, i.e. smooth curves…

Condensed Matter · Physics 2009-11-07 Weinan E , Weiqing Ren , Eric Vanden-Eijnden

Free energy calculations are widely used tools in computational chemistry, but their dependence on the assignment of partial charges during force field parametrization reduces their accuracy and reproducibility. In this work, we highlight…

This paper introduces a method for computing the Helmholtz free energy using the flow matching technique. Unlike previous work that utilized flow-based models for variational free energy calculations, this method provides bounds for free…

Computational Physics · Physics 2025-01-03 Lu Zhao , Lei Wang

We derive a fluctuation theorem for generalized work distributions, related to bijective mappings of the phase spaces of two physical systems, and use it to derive a two-sided constraint maximum likelihood estimator of their free energy…

Statistical Mechanics · Physics 2009-01-15 A. M. Hahn , H. Then

We consider the variational free energy approach for compressed sensing. We first show that the na\"ive mean field approach performs remarkably well when coupled with a noise learning procedure. We also notice that it leads to the same…

Information Theory · Computer Science 2014-10-03 Florent Krzakala , Andre Manoel , Eric W. Tramel , Lenka Zdeborova

Sampling the stationary points of a complicated potential energy landscape is a challenging problem. Here we introduce a sampling method based on relaxation from stationary points of the highest index of the Hessian matrix. We illustrate…

Statistical Mechanics · Physics 2014-07-25 Ciaran Hughes , Dhagash Mehta , David J Wales

Monte Carlo switching moves ("perturbations") are defined between two or more classical Hamiltonians sharing a common ground-state energy. The ratio of the density of states (DOS) of one system to that of another is related to the ensemble…

Computational Physics · Physics 2012-12-27 Rasmus A. X. Persson

The absolute free energy -- or partition function, equivalently -- of a molecule can be estimated computationally using a suitable reference system. Here, we demonstrate a practical method for staging such calculations by growing a molecule…

Biological Physics · Physics 2009-01-31 Xin Zhang , Artem B. Mamonov , Daniel M. Zuckerman

Most biochemical reactions in living cells are open systems interacting with environment through chemostats to exchange both energy and materials. At a mesoscopic scale, the number of each species in those biochemical reactions can be…

Optimization and Control · Mathematics 2022-11-08 Yuan Gao , Jian-Guo Liu

Estimating the free energy in molecular simulation requires, implicitly or explicitly, counting how many times the system is observed in a finite region. If the simulation is biased by an external potential, the weight of the configurations…

Chemical Physics · Physics 2021-12-22 Matteo Carli , Alessandro Laio

Sampling the free energy surface, namely, the distribution of collective variables (CVs), is a crucial problem in statistical physics, as it underpins a better understanding of chemical reactions and conformational transitions. Traditional…

Machine Learning · Computer Science 2026-05-04 Zichen Liu , Tiejun Li

A variational method for computing conformational properties of molecules with Lennard-Jones potentials for the monomer-monomer interactions is presented. The approach is tailored to deal with angular degrees of freedom, {\it rotors}, and…

chem-ph · Physics 2016-08-31 Carsten Peterson , Ola Sommelius , Bo Söderberg

Flow-based generative models have been employed for sampling the Boltzmann distribution, but their application to high-dimensional systems is hindered by the significant computational cost of obtaining the Jacobian of the flow. To overcome…

Machine Learning · Statistics 2024-07-30 Xin Peng , Ang Gao

The accurate treatment of long-range energy terms such as van der Waals interactions is crucial for reliable free energy calculations in molecular simulations. Methods like force switching, potential switching, potential shifting, and Ewald…

Chemical Physics · Physics 2025-04-21 Lindsey M. Whitmore , Yalda Ramezani , Sumit Sharma , Michael R. Shirts

Standard derivations of ``time-independent perturbation theory'' of quantum mechanics cannot be applied to the general case where potentials are energy dependent or where the inverse free Green function is a non-linear function of energy.…

High Energy Physics - Theory · Physics 2007-05-23 A. N. Kvinikhidze , B. Blankleider
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